What is a targeted therapy?
As its name suggests, a targeted therapy is a treatment capable of targeting abnormal cells specifically. An abnormal cell is a cell that is recognized as being different from other cells, or a cell that uses a known mechanism of a normal cell but in an exaggerated manner, thus becoming totally dependent on it. Used primarily in oncology, targeted therapies attack cancer cells by detecting the presence of an abnormality in them, which becomes their target. They slow down the progression of disease or even cause the tumor to regress, by specifically acting on the mechanisms that enable tumor cells to proliferate. Developed at the beginning of the 2000s, these new therapies are considered to be a small revolution in the management of cancer1.
Each year, over 18 million new cases of cancer and 9.86 million cancer-related deaths occur in the world2.
New ways to fight cancer cells
Specific molecular mechanisms are associated with each type of cancer. Thanks to progress in research, scientists are discovering more and more new molecular mechanisms which, within cancer cells or cells of the tumor microenvironment, support tumor growth and/or its propagation in the body. These discoveries make it possible to develop new types of targeted therapies that make it possible to treat more and more forms of cancer.
How targeted therapies work will differ depending on the characteristics of the disease and the effects sought.
With targeted therapies, physicians have at their disposal a new therapeutic armamentarium against cancer. Targeted therapies may be combined with conventional treatments (surgery, radiotherapy, chemotherapy), to destroy the sick cells and cause the tumor to regress, or with hormone therapy to treat hormone-dependent cancers (such as some breast cancers).
Which patients are eligible for targeted therapies?
The transformation of a normal cell into a cancer cell is the result of DNA alteration (mutations, translocations, amplifications, deletions/insertions, etc.). Also, patient eligibility for targeted therapy is based on the molecular characteristics of tumor cells, and not on the location of the tumor. Therefore, the same type of cancer in different patients will not be treated systematically with a targeted therapy. Conversely, the same targeted therapy drug may be prescribed for very different types of cancer, as long as they present the same molecular profile.
Conducting a set of molecular tests is therefore essential to determine whether it is appropriate to prescribe a targeted therapy. These tests allow the DNA of the cancer cell (collected by tumor biopsy or blood sample) to be analyzed and to screen for genetic abnormalities on which a targeted therapy may work.
The direct target can either be the genetic abnormality discovered or the molecular mechanism stimulated by the genetic abnormality. If the target of a targeted therapy drug is found, the patient can then benefit from the action of this therapy.
Targeted therapies: Course of treatment
Targeted therapies are personalized according to the molecular characteristics of the disease and the effects sought.
The small inhibitor molecules, whose aim is to act directly on cancer cells, are most of the time administered by oral route, as tablets. Monoclonal antibodies, whose mission is to act on the cancer cell environment or on their surface, are administered as an intravenous or subcutaneous injection.
The duration of the treatment depends on the type of cancer and the type of medicine(s) prescribed. In order to choose the best therapeutic strategy against the cancer to be treated, the oncologist will take into consideration the patient’s health condition, age, and environment. At the end of the treatment, tests will allow efficacy to be measured. Depending on the results, the patient may continue treatment.
Tolerance to targeted therapies
Targeted therapies work differently from conventional chemotherapies, which destroy all rapidly-dividing cells in the body (cancer cells as well as normal cells). Chemotherapies can often cause serious side effects, such as nausea, vomiting, diarrhea, fever, as well as intense fatigue and hair loss.
Targeted therapies specifically attack the cells carrying the targeted molecular abnormality and spare more healthy cells. Targeted therapies offer better tolerability in general but are not without side effects, which vary depending on the type of drug (and its mechanism of action) targeting the cancer cells. Side effects can include fatigue, gastrointestinal disorders (vomiting, diarrhea), skin problems or metabolic problems, hypertension, etc.
Therapies that offer hope
An increasing number of targeted therapies are integrated into the standard-of-care treatment for certain forms of cancer3.
Today, 1 out of 3 cancer drugs is a targeted therapy4.
These therapies bring hope to patients for the future. This is especially true since, thanks to the advances in research and an improved understanding of the mechanisms responsible for cancer cell growth, the identification of new therapeutic targets and new targeted therapy development is continuously progressing.
Targeted therapies, at the heart of precision medicine
Rounding out the existing conventional therapeutic armamentarium against cancer (surgery, radiotherapy, chemotherapy), targeted therapies and immunotherapy are part of what is referred to as “precision medicine.” Based on an improved knowledge of the biological mechanisms that lead to the appearance and development of tumors, precision medicine aims to offer each patient with cancer personalized treatment, adapted to the abnormalities of the tumor.
Today, molecular genetic testing platforms perform tens of thousands of tests every year to characterize and treat each patient in the most precise way possible. Precision medicine can only advance in the near future, with the arrival of new targeted therapies, as well as new complex drugs used as vectors to take and deliver a chemotherapy within the tumor, the development of immunotherapy, the identification of new biomarkers, or artificial intelligence, capable of predicting the evolution of certain cancers and guiding the prescription of the right treatments to the right patient at the right time.
(1) Journal of Thoracic Oncology, MS21.04 Targeted Therapy – The Second Revolution, 2018
(2) Globocan, 2020
(3) Shahid K, Khalife M, Dabney R, Phan AT. Immunotherapy and targeted therapy—the new roadmap in cancer treatment. Ann Transl Med 2019;7(20):595. doi: 10.21037/atm.2019.05.58
(4) French National Cancer Institute, 2022.